Endovascular device with membrane

ABSTRACT

Embodiments of a uniformly porous membrane covering an endoprosthetic device, for example, a stent used to treat an aneurysm, are described. Some embodiments have a pore size and spacing that provides a material ratio of between 70-80% in the deployed state. Material ratio is the proportion of the total porous segment of the membrane that corresponds to membrane material, the remainder being pores. In some embodiments, pore size ranges from about 10-100 μm. In some embodiments, pores are equidistantly spaced with pore spacing in a range of about 40-100 μm. The combination of pore size and spacing are effective to provide a membrane that substantially prevents flow to the aneurysm, while maintaining flow to perforator vessels. In some embodiments the membrane includes permanently attached agents that promote attachment of endothelial cells or progenitors and healing of the aneurysm, or reduce immune responses detrimental to the healing process.

RELATED APPLICATIONS

The present application is a continuation-in-part of U.S. patentapplication Ser. No. 11/586,899, filed Oct. 25, 2006, which is acontinuation-in-part of U.S. patent application Ser. No. 10/580,139,filed May 19, 2006, which is filed under 35 U.S.C. § 371 as a U.S.National Stage Application of PCT International Patent Application No.PCT/SG2004/000407, filed Dec. 13, 2004, which claims priority toSingapore Patent Application No. SG200401735-6, filed Mar. 31, 2004; thepresent application is also a continuation-in-part of U.S. patentapplication Ser.No. 11/637,188, filed Dec. 12, 2006, which claimspriority to Singapore Patent Application SG200508026-2, filed Dec. 13,2005; the present application is also a continuation-in-part of PCTInternational Patent Application No. PCT/SG2006/000028, filed Feb. 13,2006; the contents of each of the aforementioned applications are herebyincorporated by reference herein in their entireties.

FIELD OF THE INVENTION

The invention concerns an endovascular device for insertion into a bodyvessel to treat a diseased, damaged or weakened portion of a vesselwall.

BACKGROUND OF THE INVENTION

Vascular diseases include aneurysms causing hemorrhage, atherosclerosiscausing occlusion of blood vessels, vascular malformation and tumors.Vessel occlusion or rupture of an aneurysm within the brain can resultin stroke. Aneurysms fed by intracranial arteries can grow within thebrain to a point where their size can also cause a stroke or thesymptoms of a stroke, requiring surgery to remove the aneurysm, or otherremedial intervention.

Occlusion of coronary arteries is a common cause of heart attack.Diseased and obstructed coronary arteries result in restricted bloodflow in the heart which can lead to ischemia or necrosis. While theexact etiology of sclerotic cardiovascular disease is still in question,the treatment of narrowed coronary arteries is more defined. Surgicalconstruction of coronary artery bypass grafts (CABG) is often the methodof choice when there are several diseased segments in one or multiplearteries. Conventional open-heart surgery is of course highly invasiveand traumatic for patients undergoing such procedures. Therefore, lessinvasive procedures that accomplish the same goals are highly desirable.

One alternative method of treatment involves the use of balloonangioplasty as a way in which to reopen the lumen of an occluded vessel.In this procedure a folded balloon is inserted via a catheter into astenosed region that is either partially or fully occluding the vessellumen. Inflation of the balloon physically expands the lumen, reopeningthe occluded region, and restoring normal or at least significantlyimproved blood flow through the vessel. Alternatively, occlusiveatheromas may be cut from the inner surface, a procedure known asatherectomy. In both methods, a certain incidence of restenosis(resealing) occurs resulting in a loss of the benefit of the procedure,and potentially the need for additional rounds of therapy. Restenosisalso results in reversion back to the original occluded condition, suchthat the vessel no longer conducts a normal flow volume, which can leadto ischemia or infarct depending on the particular location and functionof the vessel in question.

A recent preferred therapy for repairing vascular occlusions involvesplacement of an expandable metal wire-frame (i.e. a stent) within theoccluded region of a blood vessel in order to keep the lumen of thevessel open. Stents are generally delivered to the desired locationwithin a vascular system by an intraluminal route, usually via acatheter. Advantages of the stent placement method over conventionalvascular surgery include obviating the need for surgically exposing,removing, replacing, or by-passing the defective blood vessel, includingheart-lung bypass, opening the chest and in some cases generalanaesthesia.

When inserted and deployed in a vessel, duct or tract (all of which canbe conveniently referred to as a vessel) of the body, for example, acoronary artery after dilation of the artery by balloon angioplasty, astent acts as a prosthesis to maintain the vessel in an open state, thusproviding a fluid pathway in the previously occluded vessel. The stentusually has an open-ended tubular form with interconnected struts as itssidewall to enable its expansion from a first outside diameter which issufficiently small to allow the stent to traverse the vessel lumen andbe delivered to a site where it is to be deployed, then expanded to asecond outside diameter sufficiently large to engage the inner lining ofthe vessel for retention at that site. The stent may be expanded via theuse of a mechanical device, for example a pressurizable balloon, oralternatively the stent may be self-expanding. Self-expanding stents canbe manufactured at a to be deployed size, and then compressed to asmaller size to enable delivery, or may be manufactured from shapememory materials that are deformable to a memorized shape in response toan externally applied energy.

Usually a stent suitable for successful interventional placement shouldbe hypoallergenic, or preferably non-allergenic, have good radio-opacityto permit radiographic visualization, free from distortion duringmagnetic resonance imaging (MRI), plastically deformable, resistant tovessel recoil, and be as thin as possible to minimize obstruction toblood flow (or other materials or fluids in vessels other than those ofthe cardiovascular system), and be relatively non-reactive in terms ofeliciting thrombogenic responses.

The typical reaction when a foreign body is implanted in a body vesselis generally negative. Foreign bodies frequently cause an inflammatoryresponse, and in the case of blood vessels, neointimal proliferationwhich results in narrowing and occlusion of the body vessel, obviatingthe benefit of the implant. As a result, both selection of the materialsfrom which the stent is composed, as well as the design of the stent,play an important role in influencing the final suitability of thedevice in practice. Therefore, in addition to the structuralrequirements for a stent to maintain a previously occluded vessel in asubstantially open conformation, stents must also be biologicallycompatible, and must be chemically stable when exposed to a biologicalenvironment.

A variety of materials have been tested and used in stents to addressthe issues of biocompatibility and material stability. For example,polyurethanes have been used in long term implants, but are not alwayssuitable for use in endovascular treatments, especially in small bloodvessels. Small blood vessels are considered to be those with an innerdiameter of 2.0 to 5.0 mm. In addition, many commercially availablepolymers are with additives, or have impurities, that are surface-activeand so reduce their usefulness in some biological applications.

More recently, polymers have been developed which can be furthermodified by the covalent attachment of various surface-modifying endgroups, these end groups reducing the reactivity of the material withcells and other factors that function in the immune response. End groupscan also be useful in providing greater chemical stability to thematerial, reducing degradation and improving the longevity of theprosthesis. For example, U.S. Pat. No. 5,589,563 (Ward & White)discloses a series of biomedical base polymers with covalently attachedend groups that give the polymer certain desirable properties. Thesemodified polymers possess surface properties that improve thebiocompatibility and overall performance of objects fashioned from them.

In addition to their biomechanical functionality, implantable medicaldevices like stents have been utilized for delivery of drugs orbioreagents for different biological applications. U.S. Pat. No.5,891,108 (Leone et al.) discloses a hollow tubular wire stent withholes through which an active substance can be delivered to a site in avessel. In some cases the drugs or bioreagents can be coated directlyonto the surface of the implantable medical devices or mixed withpolymeric materials that are then applied to the surface of the devices.For example, U.S. Pat. No. 5,599,352 (Dinh et al.) discloses a drugeluting stent comprising a stent body, a layer of a composite of apolymer combined with a therapeutic substance, overlaid by a secondlayer comprising fibrin.

However, each of these methods suffers from one or more problemsincluding poor control of release or limitations of the form of drug orother reagent that can be applied. Also, these methods are unsuitablefor situations where it would be desirable to maintain the bioactivemolecule on the device rather than having it be released, in order tomaintain a relatively high local activity of the reagent of interest.

As a result, in practice, the design and use of stents in the repair ofaneurysms or other vessel defects or diseases typically represents acompromise among competing factors. First, the stent must adequatelysupport the diseased or weakened region in order to prevent rupture ofthe aneurysm or vessel, either of which could lead to seriouscomplications including death, depending on the size, location andnature of the aneurysm or defect. Second, in the case of stents use inthe repair of aneurysms, the stent must permit sufficient blood tomaintain the patency of both the parent and perforator vessels, while atthe same time limiting flow to the aneurysm proper. Generally speaking,flow of material through the framework of a stent is achieved byregulating the porosity of the stent.

Stent porosity can be managed in a number of ways. The simplest way isto manufacture the stent so that the framework itself defines theporosity of the device. However, in biological applications, regulatingmovement of materials on cellular or subcellular scale is required, andit is difficult and costly to manufacture stents that have such fineeffective pore size. Other approaches have been to cover the stentframework for example with a membrane, where the membrane is eitherimpermeable or porous as desired. U.S. Patent Application No.2006/0217799 (Mailander et al.) discloses a stent comprising a grid ormesh structure in which one or more cells of the grid are covered with amembrane. Similarly, U.S. Patent Application No. 2006/0200230 (Richter)discloses a covering for an endoprosthetic device that comprises asheath with holes of varying size and varying frequency disposed indifferent areas of the sheath.

However, a problem inherent with these designs is that they are noteasily adapted for effecting vessel wall repairs where the area ofdisease, damage or weakness can vary in size. Thus, in order tooptimally treat an aneurysm, it would be necessary to tailor the stentand its covering to more or less the precise size of the damaged area,in order to properly occlude the aneurysm site, while maintaining vesselpatency in the parent vessel and any perforator vessels. Furthermore,these designs are not optimized such that they will generally provideflow to perforator vessels that are part of the collateral circulationin the area of the diseased, damaged, or weakened vessel, while blockingflow to an aneurysm.

SUMMARY OF THE INVENTION

Thus, in some embodiments an endovascular device for insertion into abody vessel to treat an aneurysmal portion of the body vessel, theendovascular device comprises: an expandable member, expandable from afirst position to a second position, said expandable member beingexpandable radially outwardly to the second position such that an outersurface of said expandable member engages with an inner surface of thevessel so as to maintain a fluid pathway in said vessel through a lumenin the expandable member; a membrane covering at least a portion of anouter surface of said expandable member; a plurality of pores in aporous section of the membrane, the porous section having asubstantially uniform porosity over a length extending from a proximalend to a distal end of the porous section, porosity being determined bya pore spacing and a pore size; wherein the proportion of the total areaof an outer surface of the porous section that consists of membranematerial defines a material ratio; wherein the substantially uniformporosity is selected such that, when the expandable member is positionedin the body vessel, the membrane permits a flow of blood from within thelumen of the expandable member, through at least one of the pores, andinto at least one branch vessel that branches off of the body vessel;and wherein the substantially uniform porosity is further selected suchthat, when the expandable member is positioned in the body vessel, themembrane reduces blood flow to the aneurysmal portion of the vessel,promoting thrombosis at or in the aneurysmal portion.

In some embodiments, the porosity of the porous section is selected suchthat it enables enhanced endothelial cell migration and tissue in-growthfor endothelialization while substantially preventing blood circulationto the diseased, damaged or weakened portion of the vessel wall.

In some embodiments, the pore size is between about 1 μm and about 150μm.

In some embodiments, the pore size is between about 10 μm and about 50μm.

In some embodiments, the pore spacing is between about 40 μm and about100 μm.

In some embodiments, the pore spacing is between about 60 μm and about75 μm.

In some embodiments, the material ratio in an as-manufactured state isbetween about 85% and about 96%.

In some embodiments, the material ratio in a deployed state is betweenabout 25% and about 90%.

In some embodiments, the material ratio in the deployed state is betweenabout 70% and about 80%.

In some embodiments, the material ratio in the deployed state is about75%.

In some embodiments, a diameter of the device in the deployed state isbetween about 2 mm and about 5 mm.

In some embodiments, a thickness of the membrane is between about 25 μmto about 125 μm.

In some embodiments, the thickness of the membrane is measured in anas-manufactured state.

In some embodiments, a thickness of the membrane is between about 5 μmto about 25 μm.

In some embodiments, the thickness of the membrane is measured in adeployed state.

In some embodiments, the device further comprises at least onesurface-modifying end group that promotes healing of the body vesselafter the device is inserted into the body vessel.

In some embodiments, the surface-modifying end group comprises at leastone of a fluorocarbon and the combination of polyethylene glycol andsilicon.

In some embodiments, the device further comprises at least one agent,permanently attached the membrane, that promotes healing of theaneurysm.

In some embodiments, at least one permanently attached agent comprisesat least one of a peptide, a protein, an enzyme regulator, an antibody,a naturally occurring molecule, a synthetic molecule, a nucleic acid, apolynucleotide, L-PDMP, and D-PDMP.

In some embodiments, each pore has a diameter between about 30 μm andabout 40 μm, and a distance between adjacent pores is between about 60μm and about 70 μm.

In some embodiments, the aneurysmal portion of the vessel is located ator near at least one of an intracranial aneurysm, a saccular aneurysm, awide-neck aneurysm, a fusiform aneurysm, a caroticocavenous fistula, anarteriovenous malformation, a carotid artery stenosis, a saphenous veingraft, a small vessel stenosis, and a renal artery repair.

In some embodiments, the porous section can be divided into n porousregions, and wherein an outer surface area of each of the n porousregions is substantially 1/n of a total outer surface area of the poroussegment, and wherein each one of the n porous regions has substantiallythe same porosity as each of the other n-1 porous regions.

In some embodiments, n=2.

In some embodiments, n=3.

In some embodiments, n=4.

In some embodiments, n=5.

In some embodiments, the pore size is in a range between about 1 μm andabout 150 μm, and pore spacing is between about 10 μm and about 50 μm.

In some embodiments, the pore size is between about 10 μm and about 50μm, and the pore spacing is between about 60 μm and about 75 μm.

In some embodiments, an endovascular device system for insertion into abody vessel to treat an aneurysmal portion of the vessel, theendovascular device comprises: an expandable member, expandable from afirst position to a second position, said expandable member beingexpandable radially outwardly to the second position such that an outersurface of said expandable member engages with an inner surface of thevessel so as to maintain a fluid pathway in said vessel through a lumenin the expandable member; a membrane covering at least a portion of anouter surface of said expandable member; a plurality of pores in aporous section of the membrane, the porous section having asubstantially uniform porosity over a length extending from a proximalend to a distal end of the porous section, porosity being determined bya pore spacing and a pore size; wherein the proportion of the total areaof an outer surface of the porous section that consists of membranematerial defines a material ratio; wherein the substantially uniformporosity is selected such that, when the expandable member is positionedin the body vessel, the membrane permits a flow of blood from within thelumen of the expandable member, through at least one of the pores, andinto at least one branch vessel that branches off of the body vessel;and wherein the substantially uniform porosity is further selected suchthat, when the expandable member is positioned in the body vessel, themembrane reduces blood flow to the aneurysmal portion of the vessel,promoting thrombosis at or in the aneurysmal portion; and a deliverydevice, operable to deliver the expandable member to the aneurysmalportion of the vessel, onto which the expandable member is loaded priorto delivery.

In some embodiments, the pore size is between about 1 μm and about 150μm.

In some embodiments, the pore size is between about 10 μm and about 50μm.

In some embodiments, the pore spacing is between about 40 μm and about100 μm.

In some embodiments, the pore spacing is between about 60 μm and about75 μm.

In some embodiments, the material ratio in an as-manufactured state isbetween about 85% and about 96%.

In some embodiments, the material ratio in a deployed state is betweenabout 25% and about 80%.

In some embodiments, the material ratio in the deployed state is betweenabout 70% and about 80%.

In some embodiments, the material ratio in the deployed state is about75%.

In some embodiments, a diameter of the expandable member in the deployedstate is between about 2 mm and about 5 mm

In some embodiments, a thickness of the membrane is between about 25 μmto about 125 μm.

In some embodiments, the thickness of the membrane is measured in anas-manufactured state.

In some embodiments, a thickness of the membrane is between about 5 μmto about 25 μm.

In some embodiments, the thickness of the membrane is measured in adeployed state.

In some embodiments, the system further comprises at least onesurface-modifying end group that promotes healing of the body vesselafter the device is inserted into the body vessel.

In some embodiments, the at least one surface-modifying end group is atleast one of a fluorocarbon and the combination of polyethylene glycoland silicon.

In some embodiments, the system further comprises at least onepermanently attached agent to promote healing of the aneurysmal portion.

In some embodiments, the at least one permanently attached agentcomprises at least one of a peptide, a protein, an enzyme regulator, anantibody, a naturally occurring molecule, a synthetic molecule, anucleic acid, a polynucleotide, L-PDMP, and D-PDMP.

In some embodiments, each pore has a diameter between about 10 μm andabout 50 μm and the distance between adjacent pores is between about 60μm and about 75 μm.

In some embodiments, the aneurysmal portion of the body vessel islocated at or near at least one of an intracranial aneurysm, a saccularaneurysm, a wide-neck aneurysm, a fusiform aneurysm, a caroticocavenousfistula, an arteriovenous malformation, a carotid artery stenosis, asaphenous vein graft, a small vessel stenosis, and a renal arteryrepair.

In some embodiments, an endovascular device for insertion into a bodyvessel to treat an aneurysmal portion of a body vessel, the endovasculardevice comprises: means for maintaining a fluid pathway in the bodyvessel; means for covering at least part of the means for maintaining,the means for covering having a substantially uniform porosity in aporous segment of the means for covering; and wherein, when the meansfor maintaining is positioned in a body vessel, the means for coveringpermits blood flow from the fluid pathway to at least one branch vesselbranching off the body vessel, while reducing blood flow to theaneurysmal portion, and the means for maintaining supports the bodyvessel in the region of the aneurysmal portion and provides a fluidpathway in the body vessel.

In some embodiments, a method of treating a body vessel having ananeurysmal portion comprises the steps of: providing an endovasculardevice, comprising: an expandable member, expandable from a firstposition to a second position, said expandable member being expandableradially outwardly to the second position such that an outer surface ofsaid expandable member engages with an inner surface of the body vesselso as to maintain a fluid pathway in said body vessel through a lumen inthe expandable member; a membrane covering at least a portion of anouter surface of said expandable member; a plurality of pores in aporous section of the membrane, the porous section having asubstantially uniform porosity over a length extending from a proximalend to a distal end of the porous section, porosity being determined bya pore spacing and a pore size; wherein the proportion of the total areaof an outer surface of the porous section that consists of membranematerial defines a material ratio; wherein the substantially uniformporosity is selected such that, when the expandable member is positionedin the body vessel, the membrane permits a flow of blood from within thelumen of the expandable member, through at least one of the pores, andinto at least one branch vessel that branches off of the body vessel;and wherein the substantially uniform porosity is further selected suchthat, when the expandable member is positioned in the body vessel, themembrane reduces blood flow to the aneurysmal portion of the bodyvessel, promoting thrombosis at or in the aneurysmal portion; andpositioning the expandable member in the body vessel.

In some embodiments, the porosity of the membrane is selected such thatit enhances endothelial cell migration and tissue in-growth.

In some embodiments, the pore size is between about 1 μm and about 150μm.

In some embodiments, the pore size is between about 10 μm and about 50μm.

In some embodiments, the pore spacing is between about 40 μm and about100 μm.

In some embodiments, the pore spacing is between about 60 μm and about75 μm.

In some embodiments, the material ratio in an as manufactured state isbetween about 85% and about 96%.

In some embodiments, the material ratio in a deployed state is betweenabout 25% and about 80%.

In some embodiments, the material ratio in the deployed state is betweenabout 70% and about 80%.

In some embodiments, the material ratio in the deployed state is about75%.

In some embodiments, a diameter of the expandable member in the deployedstate is between about 2 mm and about 5 mm.

In some embodiments, a thickness of the membrane is between about 25 μmto about 125 μm in the as-manufactured state.

In some embodiments, a thickness of the membrane is between about 5 μmto about 25 μm in the deployed state.

In some embodiments, the method further comprises providing a membranehaving at least one surface-modifying end group that encourages healingof the body vessel after the device is inserted.

In some embodiments, the at least one surface-modifying end group is atleast one of a fluorocarbon and the combination of polyethylene glycoland silicon.

In some embodiments, the membrane further comprises at least onepermanently attached agent to promote healing of the aneurysm.

In some embodiments, the at least one permanently attached agentcomprises at least one of a peptide, a protein, an enzyme regulator, anantibody, a naturally occurring molecule, a synthetic molecule, anucleic acid, a polynucleotide, L-PDMP, and D-PDMP.

BRIEF DESCRIPTION OF THE DRAWINGS

Examples of embodiments of the invention will now be described withreference to the following drawings.

FIG. 1A illustrates an embodiment of a balloon expandable stent.

FIG. 1B illustrates another embodiment of a balloon expandable stent.

FIG. 2 illustrates a self-expanding stent.

FIG. 3 illustrates a delivery system with a stent expanded on a balloon.

FIG. 4A is a view of a stent disposed in the location of an aneurysm

FIG. 4B is a second diagrammatic view of a stent disposed in thelocation of an aneurysm.

FIG. 5 illustrates a membrane joining two stents for treating abifurcation aneurysm.

FIG. 6 illustrates a stent with a membrane having a pattern of pores.

FIG. 7 illustrates a stent having polymer strips.

FIG. 8 illustrates a stent with a membrane having a mesh.

FIG. 9 illustrates a membrane secured to the struts of a stent.

FIG. 10 illustrates a membrane before the stent is deployed.

FIG. 11 illustrates a membrane flipping in side the vessel rather thanstaying close to the vessel wall.

FIG. 12 illustrates a stent partially covered by a membrane havingpockets for release of therapeutically effective agents.

FIG. 13 illustrates a stent with a membrane secured at three differentpositions and with three different sizes.

FIG. 14 illustrates a sleeve as a membrane supported by two ring-likestents.

FIG. 15 illustrate one embodiments of a membrane showing porepositioning.

FIG. 16 illustrates equidistantly spaced pores.

FIG. 17 illustrates a macroporous membrane.

FIG. 18 illustrates a microporous membrane.

FIG. 19A is a graphical representation of a membrane as manufactured,(i.e. unexpanded) state.

FIG. 19B illustrates a membrane in the expanded (i.e. deployed) state.

FIG. 20 illustrates an experimental model for inducing aneurysms usingelastase delivered by a catheter.

FIG. 21A illustrates a radiographic view of an aneurysm prior totreatment of an experimentally induced aneurysm.

FIG. 21B illustrates a radiographic view of the same aneurysm, 137 daysafter the start of treatment with an embodiment of a membrane-coveredstent.

FIG. 21C is a histological section taken at the level of a thrombosedaneurysm.

FIG. 22 diagrams progressive remodeling of an aneurysm afterimplantation of a stent.

FIG. 23 is a graph of the relationship between coverage ratio and stentdiameter.

FIG. 24A is a radiographic view of an aneurysm located in the subclavianartery of a rabbit.

FIG. 24B is the artery shown in FIG. 25A subsequent to treatment.

FIG. 25A is an image of a chronic angiograph of iliac arteries showingthe patency of vessels implanted with the endovascular device having asolid membrane made from a polyurethane based material with fluorocarbonsurface-modifying end groups.

FIG. 25B is an image of a chronic angiograph of iliac arteries showingthe patency of vessels implanted with the endovascular device having aporous membrane made from a polyurethane based material withfluorocarbon surface-modifying end groups.

FIG. 26 illustrates an embodiment comprising a membrane havingpermanently attached agents.

FIG. 27 is a diagrammatic view of a stent with a membrane being used totreat a bifurcation aneurysm in a first example.

FIG. 28 is a diagrammatic view of a stent with a membrane being used totreat a bifurcation aneurysm in a second example.

FIG. 29 is a diagrammatic view of a stent with a membrane being used totreat a bifurcation aneurysm in a third example.

DETAILED DESCRIPTION OF THE INVENTION

Implantable medical devices include physical structures for deliveringdrugs or reagents to desired sites within the endovascular system of ahuman body. These devices may take up diversified shapes andconfigurations depending upon specific applications. Common implantablemedical devices include stents, vena cava filters, grafts and aneurysmcoils.

The endovascular system of a human body includes blood vessels, cerebralcirculation system, tracheo-bronchial system, the biliary hepaticsystem, the esophageal bowel system, and the urinary tract system.Although exemplary stents implantable in blood vessels are described,they are applicable to the remaining endovascular system. Embodiments ofthe invention, some of which are described herein are readily adaptablefor use in the repair of a variety of vessels, including but not limitedto, treatment or repair in cases of aneurysm, ischemic stroke, carotidartery stenosis, saphenous vein graft, small vessel stenosis, or renalartery repair.

Stents are expandable prostheses employed to maintain vascular andendoluminal ducts or tracts of the human body open and unoccluded. Forexample, stents are now frequently used to maintain the patency of acoronary artery after dilation by a balloon angioplasty procedure. Astent is a typically a tubular meshwork structure having an exteriorsurface defined by a plurality of interconnected struts and spacesbetween the struts. The tubular structure is generally expandable from afirst position, wherein the stent is sized for intravascular insertion,to a second position, wherein at least a portion of the exterior surfaceof the stent contacts and engages the vessel wall where the stent hasbeen placed.

The expanding of the stent is accommodated by flexing and bending of theinterconnected struts throughout the structure. The force for expansioncan be applied externally as from a inflated balloon onto which thestent is loaded prior to placement, or the stent itself may beself-expanding. A myriad of strut patterns are known for achievingvarious design goals such as enhancing strength, maximizing theexpansion ratio or coverage area, enhancing longitudinal flexibility orlongitudinal stability upon expansion, etc. One pattern may be selectedover another in an effort to optimize those parameters that are ofparticular importance for a particular application.

Illustrated in FIGS. 1A and 1B are two exemplary balloon expandablestent designs. FIG. 1A shows a tubular balloon expandable stent 100,further comprising end markers 103 to increase visibility of the stent100 when viewed in situ using radiologic techniques. In someembodiments, the stent 100 is made of multiple circumstantial rings 101,where the ring connectors 102 connect two or three adjacent rings 101and hold the rings in place. In FIG. 1A the end marker 103 is shown as adisc-shape. The shape of an end marker 103 is not critical to thefunction of the stent 100, and will be useful as long as the shapeselected is effective to increase the radiographic visibility of thestent 100.

FIG. 1B illustrates a tubular balloon expandable stent 104, similar tothe stent 100 shown in FIG. 1A, with the exception that the stent 104comprises center markers 105, 106. The center markers 105, 106 help toaid in placing the stent over an aneurysm opening during an implantationoperation. The center markers 105, 106 can be of the same material andshape as the end markers 103.

FIG. 2 illustrates a self-expanding stent 107 made of wires or ribbons.While a self-expanding stent may have many designs, the stent 107 shownin FIG. 2 has a typical braided pattern 108 with welded ends 109. Thestent 107 is designed to be relatively flexible along its longitudinalaxis, to facilitate delivery through tortuous body lumens, but is stillstiff and stable enough radially in the expanded state, such that itwill serve to maintain the patency of a vessel lumen when implanted, forexample in the lumen of an artery.

Illustrated in FIG. 3 is a delivery system and an expanded tubular stent112, loaded over an expandable balloon 114. When the tubular stent 112is fully expanded to its deployed diameter by inflation of the balloon114, the latticework of struts takes on a shape in which adjacent crestsundergo wide separation, and portions of the struts take on atransverse, almost fully lateral orientation relative to thelongitudinal axis of the stent. Such lateral orientation of a pluralityof the struts enables each fully opened cell to contribute to the firmmechanical support offered by the stent in its fully deployed condition,and insures a rigid structure that is highly resistant to recoil of thevessel wall following stent deployment.

While a stent 112 may be deployed by radial expansion under outwardlydirected radial pressure exerted, for example, by active inflation of aballoon 114 of a balloon catheter on which the stent is mounted, thestent 112 may be self-expandable. In some instances, passive springcharacteristics of a preformed elastic (i.e., self-opening) stent servethe purpose, while in others shape memory materials are used, such thatupon activation by the appropriate energy source, the stent deforms intoa pre-determined memorized shape. Regardless of design, in all cases thestent is expanded to engage the inner lining or inwardly facing surfaceof the vessel wall with sufficient resilience to allow some contraction,but also with sufficient stiffness to largely resist the natural recoilof the vessel wall following deployment.

Referring to the delivery system depicted in FIG. 3, there is included aguide wire lumen 110, a balloon inflating lumen 111, a connector 116, aballoon catheter shaft 113, and platinum marker bands 115 on thecatheter shaft 113. The guide wire lumen 110 is used for introducing aguide wire in a balloon catheter, and the balloon inflating lumen 111for inflating the balloon after the stent has been placed at a desiredlocation. The connector 116 is used for separating the guide wire lumen110 and the balloon inflating lumen 111. The balloon catheter shaft 113carries the guide wire lumen 110 and the balloon inflating lumen 111separately, with a typical length of about 135-170 cm. The ring markers115 on the catheter shaft 113 are used so that the start of balloontapers and the edges of the stent can be visualized by X-ray.

In FIG. 3, an expanded stent 112 is shown mounted onto an expandedballoon. Conveniently, the delivery catheter can be a conventionalballoon dilation catheter used for angioplasty procedures. The ballooncan be formed of suitable materials such as irradiated polyethylene,polyethylene terephthalate, polyvinylchloride, nylon, and copolymernylons such as Pebax™. Other polymers may also be used. In order for thestent to remain in place on the balloon during delivery to the desiredsite within an artery, the stent is typically crimped onto the balloon .However, the precise design choices in delivery systems are not limitingto the scope of the disclosure.

In some embodiments, the delivery of the stent is accomplished asfollows. The stent is first mounted onto an inflatable balloon on thedistal extremity of the delivery catheter, and the stent is mechanicallycrimped onto the exterior of the folded balloon. The catheter/stentassembly is then introduced into the vasculature through a guidingcatheter. A guide wire is disposed across the diseased arterial sectionand then the catheter/stent assembly is advanced over the guide wirethat has been placed in the vessel until the stent is substantiallylocated at the site of the diseased or damaged portion of the vessel. Atthis point, the balloon of the catheter is inflated, expanding the stentagainst the artery. The expanded stent engages the vessel wall, whichserves to hold open the artery after the catheter is withdrawn.

Due to the formation of the stent from an elongated tube, the undulatingcomponent of the cylindrical elements of the stent is relatively flat intransverse cross-section, so that when the stent is expanded, thecylindrical elements are pressed into the wall of the vessel and as aresult do not significantly interfere with the blood flow through thelumen. The cylindrical elements of the stent, which are pressed into thewall of the vessel, will eventually be overgrown with a layer ofendothelial cells, further minimizing interference with blood flow thatcould be caused by the presence of the stent in the lumen. The closelyspaced cylindrical elements, located at substantially regular intervals,provide uniform support for the wall of the artery, and consequently arewell adopted to tack up and hold in place small flaps or dissectionsthat may exists in the vessel wall.

Resilient or self-expanding prostheses can be deployed without dilationballoons. Self-expanding stents can be pre-selected according to thediameter of the blood vessel or other intended fixation site. Whiletheir deployment requires skill in stent positioning, such deploymentdoes not require the additional skill of carefully dilating the balloonto plastically expand the prosthesis to the appropriate diameter, as thefinal diameter will be primarily a function of the stent design itself.Further, the size of the self-expanding stent is chosen such that whenin place it remains at least slightly elastically compressed, and thushas a restoring force which facilitates acute fixation. By contrast, aplastically expanded stent must rely on the restoring force of deformedtissue, or on hooks, barbs, or other independent fixation elementsincluded as part of the stent structure.

Self-expanding stents can be fashioned from resilient materials such asstainless steel, and the like, wherein the stent is loaded onto thedelivery device in a compressed state, and upon placement at the desiredlocation is allow to naturally elastically expand. Expandable stents canalso be fashioned from shape memory materials such as nickel-titaniumalloys and the like, wherein the stent is expanded from a first shape toa second shape by activation with an energy source such as heat,magnetic fields or an RF pulse for example.

The presence of a foreign object in a vessel, like a stent, can promotethrombus formation as blood flows through the vessel, and plateletscontact the stent surface. This is a well-recognized problem in otherareas of cardiovascular treatment, such as when artificial heart valvesare implanted. In serious instances, clot formation can lead to acuteblockage of the vessel. In addition, as the outward facing surface ofthe stent in contact or engagement with the inner lining of the vessel,tissue irritation can lead to an inflammatory reaction, furtherexacerbating restenosis due to localized hyperplasia. Stent design anduse must take into account all these myriad factors.

In one embodiment, illustrated in FIG. 4A, and 4B, there is provided anintracranial stent 202 and for use in the repair of stenotic lesions andaneurysms 201. Due to the characteristics of intracranial blood vessels,the intracranial stents 202 are designed to be very flexible, lowprofile (diameter of 0.8 mm or less when crimped onto the deliverycatheter) and having a thin wall (less than 0.1 mm). As they are used insmall vessels, intracranial stents 202 do not necessarily possess, orneed, the highest possible radial strength.

As shown in FIG. 4A, the intracranial stent 202 is located at the siteof an aneurysm 201. A membrane 203 partially covers the stent 202 and ispositioned to seal the neck, thus blocking blood flow to the aneurysm201. Blocking blood flow is an important function of the stent, as itreduces the risk of aneurysm rupture, which can cause neurologicaldeficit or even death if it occurs intracranially, and promotes theformation of a thrombus and resolution of the aneurysm. Radiopaquemarkers 204 can be located in the middle of the stent 202 to providevisibility of the stent 202 during operation and post-operationinspection.

In FIG. 4B, a portion of the stent 202 is shown to include open “cells”205. This design avoids blocking perforator vessels (sometimes calledperforators), small capillary vessels that have important anddistinctive blood supply functions. It is possible that tubular stentscan block perforators and inhibit important functions of these vessel,which may be related, but not limited the general health of the vesseland surrounding tissue. Moreover, stents covered with non-porousmembranes suffer from the disadvantage that the membrane portion of thestent can block the perforators.

Stents may also be used to treat a number of different types ofaneurysms, including bifurcation aneurysm, as shown in FIG. 5. Forexample, as illustrated, an intracranial aneurysm 201 can be treatedwith a stent 202 and membrane 203 to effectively prevent ischemic andhemorrhagic stroke. At least 30 to 35% of aneurysms are located atbifurcation sites of intracranial vessels. In this embodiment, themembrane 203 is one-sided and non-circumferential. In some embodimentsthe membrane may be circumferential and may cover substantially theentire stent. The stents 202 are joined by the membrane 203, whichcovers the aneurysm neck 201. The same pattern can be applicable toself-expandable (super-elastic) or balloon expandable (stainless steel,CoCr, PtIr alloys) stents. Thus, the intracranial stent 202 coupled witha membrane 203 acts as a scaffold to open clogged arteries, and themembrane provides a cover to prevent blood flow to the aneurysm 201.Obstructing blood supply to the aneurysm 201 isolates the aneurysm 201from normal blood circulation, eventually resulting in thrombusformation within the aneurysm. Complete obstruction of the aneurysm 201may not be necessary in order to achieve initiation of an aneuryticthrombus.

Table 1 provides a table with exemplary dimensions for an intracranialstent 202 designed for use with a membrane 203. The membrane 203 isbiocompatible, has good adhesion to stent struts made from a variety ofmaterials including, but not limited to stainless steel, titanium andnickel alloys and the like. The membrane forms an ultra-thin film thatis porous as opposed to being a solid film, having holes or poresincluded during the process of manufacturing the membrane. In someembodiments, the pore size and material coverage area are selected toprevent blockage of perforator vessels, and while restricting blood flowto the aneurysm. TABLE 1 Typical Dimensions of Manufactured Stents forIntracranial Use As Dimensions Manufactured Crimped Expanded StrutThickness 0.003″ (0.076 mm) Outer Diameter 0.080″ (2.03 mm) 0.040″ (1.02mm) 0.16″-0.20″ (4.0-5.0 mm) Distance 0.031″ (0.80 mm) 0.016″ (0.40 mm)0.079″ (2.0 mm) Between Struts

In some embodiments, the membrane 203 is made from a thin film generallyin a range of from about 25 μm to about 125 μm in thickness, measured inthe as-manufactured state, and is from about 5 μm to about 25 μm thick,as measured in the deployed state (expanded state). The film has goodexpandability, and can be expanded up to about 400% using relatively lowforce. The membrane 203 also has good chemical stability at ambientconditions allowing for extended storage prior to use, and is stableunder sterilization conditions (ethanol). Examples of physicalproperties of the membrane are a hardness of about 75A (measured with aShore durometer), tensile strength up to about 7500 p.s.i., andelongation of up to about 500%.

Conveniently, membranes can be made porous, and if desired uniformlyporous, by drilling holes into a solid film. In this way a stent 202covered by a uniformly porous membrane 203 can be provided asillustrated in FIG. 6. The exploded view of FIG. 6 depicts an area of amembrane having uniformly spaced pores. The pore diameter is generallyin the range of about 1-150 μm, while the distance between pores isgenerally less than about 100 μm. Porosity of a stent 202 covered by amembrane can be varied in other ways, including covering the stent 202with membrane strips as shown in FIG. 7, or by providing a stent 202covered with a mesh like membrane 203, as in FIG. 8. Porosity can alsobe varied by changing pore diameter, or the number of pores per unitarea of the membrane.

Where the stent is covered with membrane strips, as shown in FIG. 7, thestrips of membrane 203 can be wrapped laterally around the stent 202.Securing the strips to the stent 202 may be accomplished by interlacingthe strips above and below the struts of the stent (not shown).Typically the width of strips would be less than 0.075 mm, and thedistance between adjacent strips would be less than about 100 μm.

Where a mesh or woven membrane is used, a sheet of woven membrane 203can be wrapped circumferentially around the stent 202, as illustrated inFIG. 8. In one embodiment the mesh size is about 0.025 to 0.05 mm, whilethe width of the polymer is typically less than about 100 μm.

In some embodiments, the membrane 203 completely surrounds the stentstruts, and forms a stable film between the struts, as shown in FIG. 9Aand B. The film between struts can be disposed centrally between strutsas in FIG. 9A, or outside struts as shown in FIG. 9B. FIG. 10illustrates a membrane and stent in the unexpanded state, prior todeployment. Where the film is located outside the struts, as in FIG. 9B,there is a further advantage provided in that the membrane will tend tomaintain closer contact with the vessel wall, and will avoid “flipping”toward the inside the vessel, as is depicted in FIG. 11.

Implantable medical devices can also be used to deliver drugs orreagents to specific locations within the vascular system of a humanbody. As shown in FIG. 12, a membrane 203 can comprise pockets 208 whichserve as reservoirs for drugs or reagents intended for delivery into theregion of a vessel wall or lumen. In certain embodiments, the membrane203 comprises a first layer 206 attached to the outer surface of animplantable medical device such as a stent 202. An intermediate layer isattached to the first layer wherein the intermediate layer comprises atleast two circumferential strips being separated from each other and asecond layer covering the first layer and the intermediate layer.

The spaces surrounded by the first layer, and the circumferential stripsand the second layer form the pockets 208 that serve as receptacles fordrugs or reagents. In other embodiments, the intermediate layer includesat least one opening so that the pockets can be formed within theopenings. The shapes and sizes of the openings can be varied inaccordance with specific applications. The stent 202 can be partiallycovered by a membrane 203 that comprises a first layer 206 and a secondlayer 207.

In some embodiments, the membrane 203 can cover the entire stent, orportions of the stent 202, as is shown in FIG. 13. Thus, the size of themembrane can be varied if desired to particularly suit the locationwhere the stent is to be placed.

Many polymeric materials are suitable for making the layers of themembrane 203. Typically, one first layer is disposed onto the outersurface of a stent. The first layer has a thickness of about 50-125 μm,with pore sizes of about 20-30 μm as a nominal initial diameter. Incertain embodiments, the first layer can serve as an independentmembrane 203 to mechanically cover and seal the aneurysm 201. The firstand/or second layers can be comprised of biodegradable material, andfunction as a drug or reagent carrier in order to provide sustainedrelease functionality.

It is desirable that the intermediate layer be formed of a materialwhich can fuse to the first and second layers or attached to the firstlayer in a different manner. In certain embodiments, the intermediatelayer may be merged with the first layer to form a single layer withrecessions within the outer surface of the merged layer. The second andintermediate layers can be made of biodegradable material that includedrugs or other reagents for immediate or sustained release. After thebiodegradable material is dissipated through the degradation process,the membrane 203 is still intact, providing vessel support. The secondlayer can also be composed of a polymeric material. In some embodiments,the second layer has a thickness of about 25-50 μm, with pore sizesranging from about 70-100 μm.

The polymeric layers may be fashioned from a material selected from thegroup consisting of fluoropolymers, polyimides, silicones,polyurethanes, polyurethanes ethers, polyurethane esters,polyurethaneureas and mixtures and copolymers thereof. Biodegradablepolymers can include polylactide, poly(lactide-co-glycolide),poly-orthoesters, polyphosphazenes, polyanhydrides, orpolyphosphoesters. The fusible polymeric layers may be bonded byadhering, laminating, or suturing. The fusion of the polymeric layersmay be achieved by various techniques such as heat-sealing, solventbonding, adhesive bonding or the use of coatings.

Types of drugs or reagents that may prove beneficial include substancesthat reduce the thrombogenic, inflammatory or smooth muscle cellproliferation response due to the implanted device. For example, cellproliferation inhibitors can be delivered in order to reduce or inhibitsmooth muscle cell proliferation. In intracranial or some otherapplications fibrin sealants can be used and delivered to seal aneurysmneck and provide fibroblasts and endothelial cells growth. Specificexamples of drugs or reagents include heparin, phosporylcholine,albumin, dexamethasone, paclitaxel and vascular endothelial growthfactor (VEGF). This list is not exhaustive, and other factors known toregulate inflammatory responses, cellular proliferation, thrombogenesisand other processes related to reaction to foreign bodies arecontemplated to be useful within the scope of the disclosure.

The drug or reagents can be incorporated into the implantable medicaldevices in various ways. For example the drug or reagent can be injectedin the form of a gel, liquid or powder into the pockets. Alternativelythe drug or reagent can be supplied in a powder which has been formedinto a solid tablet composition, positioned in receptacles placed in thedevice.

It is at times desirable to provide a stent that is highly flexible andof small profile in order to effect treat vessels of very small caliber,for example, intracranial vessels with lumen diameters ranging in sizefrom about 1.5 mm to about 5.0 mm. High flexibility allows the stent tobe advanced along the anatomy of the intracranial circulation.

In some embodiments, as illustrated in FIG. 14, a membrane 203 isembodied as a sleeve 301 supported by two ring-like short stents 302 atboth ends of a device so that the membrane 203 covers the whole area ofthe device 302. There is no scaffold support in the middle of the device302. Radiopaque markers 303 are located at both ends of the stent 302.Depending on the particular application, the rings can be balloonexpandable and made from stainless steel or self-expandable and madefrom NiTi (memory shaped nickel-titanium alloy), and the like.

The membrane 203 is part of the stent structure and is effective toocclude the aneurysm neck and “recanalize” a diseased, damaged, orweakened vessel, leading to healing of the vessel and elimination of theaneurysm. The use of a stent as shown in FIG. 14, further obviates theneed for coiling procedures, which are at times used in conjunction withstents to treat wide neck aneurysms. The present apparatus and methodsare also a preferred treatment solution for cc fistula ruptured incavernous sinus, pseudoaneurysms, saccular aneurysms.

In some embodiments, there is provided a porous membrane as part of thedevice. The membrane 203 has a system of holes or pores 25 with porediameter 21 on the order of about 1 to 100 μm, and borders 23 betweenthe pores have a width generally less than about 100 μm, as shown inFIG. 15. To provide a membrane of variable porosity, pore spacing andeven pore size can be varied in different areas of the membrane.

It has been further discovered that a membrane having uniform porositycan be effective in blocking blood flow to an aneurysm while maintainingflow to perforator vessels.

In some embodiments, pore spacing (the distance between adjacent pores)can be in a range of from about 40 to 100 μm. To produce a membrane ofuniform porosity, pore diameter 21, and interpore spacing 22, will begenerally equidistant, as in FIG. 16, over substantially the entire areaof the membrane. Depending on the size and number of pores in themembrane, the membrane can be described as being macroporous ormicroporous. For example, in a macroporous membrane, an schematic ofwhich is shown in FIG. 17, pores 25, may range in size from about 10 to100 μm, and are relatively equally spaced within the membrane material20. Alternatively, in a microporous membrane, pore diameter may be onthe order of about 1 to 10 μm, and again are generally equally spaced ina uniformly porous section of a membrane. The pore sizes shown in FIGS.17 and 18 are only examples, and a range of pore sizes are expected tobe useful in an implantable device.

Furthermore, the characterization of a membrane as either macro-ormicroporous is not limiting to the disclosure. The functionality of themembrane is dependent on pore diameter and pore spacing, which aredescribed in terms of physical measurement units, and how the particularphysical dimensions of the membrane pores operate in situ to regulateblood flow. In either case, membranes having porous sections of uniformporosity can be fashioned by selecting a desired pore diameter and porespacing combination. As is seen in the data presented below, variouscombinations of pore diameter and pore spacing are effective to providea membrane of optimal porosity over a range of deployed sizes. Thus, aporous membrane 203 is able to significantly improve hemodynamics aroundthe aneurysm 201, since it has a lower delivery profile and is moreflexible, as compared to a stent 202 with a solid membrane.

One application for a device having a macroporous membrane is to treataneurysms within close proximity of branches or perforators. Anotherspecific application is the treatment of an intracranial saccular orwide neck aneurysm located above the ophthalmic artery where perforatorsextend from the parent artery within close proximity of the aneurysm.Microporous devices are suitable for use in areas where perfusion ofperforators is of less immediate concern. Thus, the micro-porous deviceis used for conditions which require total coverage to immediately blockblood flow, for example, a caroticocavenous fistula, or where there islittle or no risk of blocking perforators, for example, below theophthalmic artery.

The device may be used for the treatment of endovascular disease such asaneurysms, arteriovenous malformations (AVM's) and caroticocavenousfistulas. The device may also be useful in other vessel relatedapplications such as treatment or repair in cases of ischemic stroke,carotid artery stenosis, saphenous vein graft, small vessel stenosis, orrenal artery repair. The pore patterns are designed with considerationof factors such as specific flow conditions of blood vessels, and thelocation of the vessel being repaired.

The design of the porous section of a membrane is therefore initiallydetermined according to the intended application of the device, andthree main factors, pore size 21, bridge dimensions 22, 23, and materialratio of the membrane. Pore size 21 can be measured in the “as designedand manufactured” (i.e. unexpanded) and “as deployed” (i.e. expanded)states. Typically, pore size in the unexpanded state is about 1.5 to 2.5times smaller than pore size after the membrane has been expanded to itsdeployed size. This is depicted in FIG. 19A and B.

Bridge dimensions 22, 23 refer to the shortest distance separating onepore 25 from its adjacent pores, as shown in FIG. 15. Each 25 may bespaced from adjacent pores at variable distances, or as shown in oneembodiment depicted in FIG. 16, at generally equal distance. In auniformly porous section of a membrane the pore spacing will berelatively equidistant throughout the membrane. Similar to pore size 21,bridge dimensions 22, 23 can also be measured in two states, as designedand manufactured, or as deployed. The as designed and manufacturedbridge dimensions are typically larger than the as deployed bridgedimension 22, 23 by a factor of 1 to 2, since stretching of the membraneduring deployment reduces the size of the bridge.

Membrane Porosity

The relative porosity of a porous section of a membrane will be dictatedby the size of individual pores and the number of pores per unit area(i.e. pore density). As used herein, the term “porous section” refers tothat area of a membrane that includes substantially all the pores of themembrane. Coverage and porosity can both be described in terms of arelationship between the area of the apparent area of the porous sectionof the membrane corresponding to membrane material, versus thatcorresponding to the pores. Thus, the material ratio is the fraction ofa membrane area that corresponds to membrane material, or in otherterms, total apparent area or the porous section (100%) —pore area(%)=material ratio (%). As used herein, the term “material ratio” refersin particular to the membrane material versus pore area in a poroussection of a membrane.

As indicated, material ratio is conveniently expressed as a percentage.So, for example, a membrane lacking pores has a material ratio=100%,while in a membrane with 20% of its total area encompassed by pores, thematerial ratio=80%. Likewise, porosity can also be expressed as apercentage, where porosity (%)=total area of the porous section of themembrane (100%)—material ratio (%). A membrane having a material ratioof 75% would have a porosity of 25%. Both material ratio and porositycan be described in membranes in the “as manufactured” and “as deployed”stages. In some embodiments, the overall material ratio in the deployedstate can range between about 25% to about 80%.

It has been discovered that a membrane of uniform porosity can beeffective to promote healing of an aneurysm if the material ratio of theporous section of the membrane is within a certain range when themembrane is in the deployed state. Thus, in some embodiments thematerial ratio of the porous section of the membrane is preferably in arange between about 70% to 80%, with the optimal material ratioconsidered to be about 75%, when the membrane is deployed. Uniformity isachieved by maintaining the variance in the size of pores, as well asthe spacing between pores in a porous section of the membrane, while anoptimal material ratio is achieved on the basis of particular porediameters and spacing.

The porous section can also be conceptually divided into a number (n) ofporous regions, wherein the area of each of the n regions issubstantially 1/n of the total area of the porous section of themembrane. For example, in some embodiments, there can be 2, 3, 4, 5 ormore porous regions, where each of the regions has substantially thesame porosity as each of the other porous regions existing with theporous section of the membrane. The porosity of either a region or theporous section as a whole is determined by the combination of pore sizeand pore spacing.

While the interpore size variance will be substantially uniform over thearea of a porous section within each individual membrane, it is to berecognized that it is possible to provide different membranes withdifferent numbers of pores, or different pore spacing as a way in whichto provide a set of membranes of varying porosity. In this way it ispossible to have a set of membranes with a range of porosities, any oneof which can be chosen based on the requirement in a particularapplication. Thus depending on a variety of factors, a membrane could beproduced with properties that would make it particularly well-suited foruse in aiding in the stabilization and repair of a particular vessel,while for another application a membrane of a different porosity mightbe preferable, and could be fashioned accordingly.

Porosity of the membrane is considered optimal when the membrane permitsblood supply to perforators of main arteries while reducing bloodcirculation to the diseased, damaged or weakened portion of the vesselwall being repaired. In addition, a further benefit may be realized byselecting a membrane having a porosity that enables enhanced endothelialcell migration and tissue ingrowth for faster endothelialization. Themembrane as disclosed may be used in devices designed for a variety ofvessel repair applications other than aneurysms. These may include, butare not limited to, use in the treatment of ischemic stroke, carotidartery stenosis, saphenous vein graft, small vessel stenosis, or renalartery repair.

As indicated above, part of the novelty described in the presentdisclosure lies in the discovery that a stent having a uniformly porousmembrane is capable of supporting a vessel wall at the site of ananeurysm, maintaining the patency of parent and perforator vessels,while restricting blood flow to the aneurysm itself. In prior artdevices these functionalities were achieved using membranes withnon-uniform porosity, or regions of varying porosity. By providing thesefeatures the device promotes more rapid and more effective healing of ananeurysm, while at the same time providing a device that is moreuniversally adaptable for use in a wider variety of in vivo locationsthan previously possible, and simpler to manufacture and use.

This has been confirmed experimentally in an animal aneurysm model. Inthis model system, aneurysms are induced by infusion of elastase intothe lumen of a vessel by way of a catheter, as diagrammed in FIG. 20(See: Miskolczi, L. et al., Rapid saccular aneurysm induction byelastase application in vitro, Neurosurgery (1997) 41: 220-229;Miskolczi, L. et al., Saccular aneurysm induction by elastase digestionof the arterial wall, Neurosurgery (1997) 43: 595-600). An exampleaneurysm 200 produced by this method is shown in FIG. 21A.

In the illustrated experiment, a stent was deployed at the site of theaneurysm shown in FIG. 21A, in order to support the vessel wall and toaid in repair of the damaged area. As can be seen in FIG. 20B, after 137days blood flow to the aneurysm had ceased, while the patency and flowin the parent vessel 210 and a nearby perforator vessel 220 wasmaintained. A histological section through the vessel at the site of theaneurysm, shown in FIG. 21C, reveals that a thrombus 240 formed at thesite of the aneurysm, indicating that the aneurysm had becomesubstantially occluded. Note that the parent vessel 210 is open andunobstructed. This process of remodeling of the aneurysm is diagrammedin FIG. 22.

Results from a series of studies like these have suggested that thematerial ratio of the membrane for optimal efficacy should be about 75%,or at least in the range of about 70-80%. In order to achieve thisoptimal porosity, several factors are considered. For example, the sizeas manufactured relative to the deployed size will be important, as thechange in pore area occurs at a different rate than does the overallarea of the membrane.

The material ratio has therefore been determined for membranes ofvarying pore diameter, pore spacing, and degree of expansion from themanufactured size to various deployment sizes, in order to evaluate whatpore spacing and pore size can provide a material ratio in the range ofabout 70-80%, at deployed sizes ranging from 2.5-5.0 mm. In the examplesdescribed, material ratio in the unexpanded state ranged from 86-96%depending on the pore size and spacing. To determine the material ratioin the expanded state, membranes were expanded as they would be duringdeployment, and the pore diameter measured at selected areas. Thematerial ratio was then determined as follows:A=total area of porous section of membrane; P=total area of pores;Porosity=(P÷A)×100%; Material Ratio=(1−(P÷A))×100%

In the data shown in Table 2, two membranes having porous sections withdifferent pore size and pore spacing were evaluated. Macroporous 30/70(30/70 membrane) refers to a membrane manufactured with 30 μm pores withan interpore spacing of 70 μm in the unexpanded state; likewise,Macroporous 40/60 (40/60 membrane) refers to a membrane with 40 μm poresand an interpore spacing of 60 μm, again, in the unexpanded state. TABLE2 Effect of Deployment Size on Material Ratio Diameter of Stent 2.0 mmConfiguration (as made) 2.5 mm 3.0 mm 3.5 mm 4.0 mm Macroporous 30/7092% 87% 80% 75% 69% Pore Diameter: 30 μm Pore Spacing: 70 μm Macroporous40/60 86% 78% 72% 64% 56% Pore Diameter: 40 μm Pore Spacing: 60 μm

As the data in Table 2 shows, when a membrane is expanded from itsmanufactured size (here 2.0 mm) to various deployed sizes, ranging from2.5 to 4.0 mm, the material ratio decreases. Thus, depending on theinitial pore size and density, the optimal material ratio of about70-80% will be achieved at different degrees of expansion, analogous tothe various deployment diameters of the stent being covered by themembrane.

For example, in a 30/70 membrane, material ratios within the optimaldesired range of about 70-80% are substantially achieved at deploymentdiameters of about 3.0 to about 4.0 mm, when starting with amanufactured size of 2.0 mm. For a 40/60 membrane the optimal materialratio is achieved at a point between 2.0 to 2.5 mm, up to about 3.0 to3.5 mm.

By extending this analysis it is possible to determine the number ofdifferent stent pore patterns, the pattern being the combination of poresize and interpore spacing, necessary to provide about a 70-80% materialratio over wide range of stent diameters. The goal is to knowbeforehand, the combination of pore size and spacing that, when themembrane is expanded to its deployed size, will provide a material ratiowithin the desired range of about 70-80% and preferably about 75%.

For example, the calculations in Table 3 show that with three differentmembrane patterns, it is possible to achieve a material ratio in therange of about 70-80% using a stent with a manufactured size of 2.2 mm,expanded to deployment sizes ranging from 2.5-5.0 mm. In these cases,the material ratio of the membrane in the unexpanded state ranges from86-96%. TABLE 3 Relationship of Material Ratio and Stent Diameter FinalPore Interpore % coverage % coverage as diameter diameter, distance, asmanufactured of patch Stent size μm μm deployed at 2.2 mm 2.5, 2.75, 3.0mm 2.5/3.0 mm 40 60 70-80% 86% 3.25, 3.5, 3.75, 4.0 mm 3.5/4.0 mm 30 7070-80% 92% 4.25, 4.5, 4.75, 5.0 mm 4.5/5.0 mm 20 75 70-80% 96%

These results are further exemplified in FIG. 23, which shows a graphicanalysis of the relationship between pore diameter, pore spacing anddeployment size for three different pore patterns, and the materialratio that results upon deployment to various diameters. In each casethe material ratio of the membrane is plotted as a function of diameterof the stent in the expanded state. In all cases, the stents aremanufactured at a size of about 2.2 mm. A surgeon, simply by knowing thesize of the vessel to be repaired, can readily select a stent andmembrane combination optimized to provide a 70-80% material ratio withina porous section of the membrane when the device is deployed, andachieve effective healing and repair of an aneurysm.

As shown in FIG. 23, for a 40/60 membrane, deployment sizes ranging fromabout 2.7 mm to about 3.5 mm will provide a coverage area in the desiredrange of about 70-80%. For a 30/70 membrane, deployment diametersranging from about 3.5 mm to about 4.5 mm will result in a coverage areain the desired range of about 70-80%, and for a 20/75 membrane (i.e. 20μm pore diameter; 75 μm pore spacing) deployment sizes ranging fromabout 4.2 mm to about 5.4 mm will provide a coverage area in the desiredrange of about 70-80%. Thus, a material ratio in the range of about70-80% can be achieved over deployment sizes of 2.7-5.4 mm by selectingthe membrane from a set of only three membranes. It is contemplated thatby varying pore spacing and pore diameter, as well as with membranesmade from various materials, greater flexibility in obtaining optimummaterial ratio at the widest variety of deployed sizes is possible.

In practice, and as shown in FIG. 24A and B, an embodiment of a device10 effectively reduces blood flow into an aneurysm 50. Reducing flow tothe aneurysm induces intra-aneurysmal thrombosis. FIG. 24A shows ananeurysm 50 located in the subclavian artery of a rabbit. In FIG. 24B,the results show that within a few hours deployment of the device 10 inthe vessel 5, blood supply to the body of the aneurysm 50 is effectivelystopped. Significantly, the pore pattern of the membrane continues toallow an uninterrupted supply of blood through perforator vessels 55located proximal to the deployed device 10. The device 10 uses theantagonistic relationship between the sufficient reduction of bloodsupply to disrupt and thus heal an aneurysm 50 and the maintenance ofsufficient blood supply vital to keep the perforators 55 patent.

For example, consider an aneurysm 50 with aneurysm neck diameter ofabout 6 mm and height of about 10 mm. If the aneurysm neck is covered bya 25% material ratio macro-porous device 10, a reduction of 25% bloodflow into the aneurysm sac is possible, with higher material ratios, forexample 70-80%, or preferable 75%, even greater inhibition of blood flowto the aneurysm is achieved. It is expected that the percentagereduction in blood flow will exceed the simple percentage material ratiodue to the viscosity of blood, as well as further reduction of bloodflow due to flow disruption and dispersion. The geometry of the aneurysmcan also play a role in the effectiveness and operation of the device.

Lubricious Coating for Membrane and/or Stent

A lubricious layer can be optionally applied onto the outer surface ofthe stent to improve trackability during delivery of the device to thesurgical site. This coating may be applied after the device isfabricated and placed onto a delivery system or before placement ontothe delivery system. Alternatively, this layer may be introduced incombination with the membrane material as an additional surfaceproperty, by modifying the chemical structure or surface properties ofthe device to provide a device with a low surface coefficient offriction.

In some embodiments, the membrane polymer may further comprisesurface-modifying end groups such as those disclosed in U.S. Pat. No.5,589,563 (Ward & White), the entire contents of which are herebyincorporated by reference.

Lubricious coatings have been used previously in devices designed toaccess target sites in small vessels. For example, U.S. Pat. No.5,312,356 (Engelson et al.) discloses a catheter comprisinganti-friction materials to prevent an internal guide wire from stickingagainst the internal tubular surface of the catheter.

The lubricious layer may be made from, for example, hydrophilicpolyvinylpyrrolidone (PVP), and hydrophilic polymers like polyacrylateor polymethacrylate, as well as hydrogels like polyethylene oxide (PEO)may also be used. Gelatin may also be used. Preferably the layer is alsobiocompatible. It is also desirable that the layer have the optimalbalance of stability and durability to maintain integrity duringtracking.

Chemical Properties of the Membrane

The membrane is preferably made from biocompatible, highly elastomericpolymer. Polyether urethane (PEU) or polycarbonate urethane (PCU) may beused.

Trade names for PEU include Tecoflex, Tecothane, Hapflex, Cardiothane,Pellethane, and Biospan. Trade names for PCU include ChronoFlex,Carbothane, and Corethane.

In some embodiments the membrane is made from BioSpan F, a materialdeveloped by Polymer Technology Group (PTG), Berkeley, Calif., USA.BioSpan F is a polyurethane based material with fluorocarbonsurface-modified end groups. In studies performed both in vitro and invivo, this material has been shown to possess excellent compatibilityproperties matching the environment of small blood vessels. Theselection of BioSpan F for the membrane of the device in treating smallvessels is preferred due to resistance to thrombogenesis as comparedwith PET or e-PTFE membranes. Preferably, the membrane fashioned fromBioSpan F will include a specific pore pattern as described earlier toobtain better resolution and healing of the aneurysm. TABLE 4 Summary ofProtein Adsorption Test Concentration Adsorbed Test of protein foundAmount of protein Adsorbed article (μg/ml) protein (μg) (μg/cm²) protein(μg/g) BioSpan 5.5 28 1.4 230 BioSpan F 3.5 18 0.88 160 ePTFE 16 80 4.04600

Table 4 shows initial results from in vitro biocompatibility testscomparing three materials; BioSpan, BioSpan F, and ePTFE. As can beseen, BioSpan F was the least thrombogenic of the three. The results ofanimal studies, shown in FIG. 25A and B, confirm the superiorbiocompatibility of BioSpan F. An endovascular device 76 with a membranemade from BioSpan F was placed in the right iliac artery 78 (left sideof FIG. 25A). The angiographic study shows normal patency of the arteryafter healing of the implant. In contrast, an endovascular device 80,made from a different membrane material, and placed in the left iliacartery 74 of the same animal (right side of FIG. 25A), showed poorbiocompatibility, such that after healing the vessel 74 becamecompletely occluded in the region of the device 80.

Additional animal studies, shown in FIG. 25B, revealed that when BioSpanF was used as the membrane material, a stent covered with a porousmembrane 78 had a lower degree of narrowing and thus had better healingproperties than the stent covered with a solid membrane 79. With aporous membrane approximately 5% narrowing was observed (left side ofFIG. 25B), while with a solid membrane 15-20% narrowing was seen (rightside of FIG. 25B).

In some embodiments, membranes can be fashioned from materials of theBioSpan family using the same surface modifying end group technique, butwith application of different end groups. BioSpan PS, for example, is asurface modified material with PEO and silicon end groups.

Membranes With Permanently-Attached Agents

In some embodiments, one of which is illustrated in FIG. 26, the device1010 is a stent comprising struts 1011, covered by an ultra-thinmembrane or coating 1015, and where the membrane 1015 is ofsubstantially uniform porosity over its length. The membrane comprisestwo surfaces, a luminal surface and a vessel wall surface. On theluminal surface, agents 1020, 1021, 1022 are permanently attached to themembrane 1015. On the vessel wall surface, agents 1023, 1024, and 1025are permanently attached to the membrane. At least one capture agent1021 is permanently attached to the luminal surface of the membrane 1015to capture a desired target component 1030 present in the fluid passingthrough the vessel. At least one signal agent 1022 is permanentlyattached to the luminal surface of the membrane 1015 to signal thecaptured target component 1030 to up regulate or down regulate a cellfunction of the captured target component 1030 to enhanceendothelialization and healing.

The cell function being regulated can include, but is not limited to,proliferation, migration, maturation, and apoptosis. The desired targetcomponent 30 can include, but is not limited to, an endothelialprogenitor cell, in which case the signal agent 22 could up regulate therate of endothelialization, and reduce the time for inflammation andthrombosis. Conveniently it is possible to combine a membrane havinguniform porosity, with one comprising agents, 1020, 1021, 1022,permanently attached to the membrane. A membrane configured in this waywould thus be adapted to substantially prevent blood flow to ananeurysm, while maintaining blood flow to perforators, and in additioncould provided various agents that would enhance the process of healingthe aneurysm.

The pharmaceutical agents 1020, 1021, 1002, coated on the lumen side ofthe membrane 1015, prevent the occlusion of the original patent lumen.In some embodiments, the capture and agent 1021 is arranged in a firstconformation of a single arm structure made of an organic linkeranchored to the membrane 1015. The organic linker may be a short chainof organic molecules anchored on one end to the membrane 1015, and theother end bound to the agent molecule that captures specific endothelialcells from the blood to promote endothelialization. The capture andsignal agents 1020, 1021, 1022 are arranged in a second conformation ofa branched structure made up of an organic linker anchored to themembrane 1015. The capture agent 1021 specifically captures endothelialprogenitor cells similar to the other capture agent 1020, while a signalagent 1022 enhances endothelial cell alignment and proliferation.Alternatively, the signal agent 1022 is arranged in a first conformationof a single arm structure made up of an organic linker anchored to themembrane 1015.

On the vessel wall side of the membrane 1015, a third pharmaceuticalagent 1023 is permanently attached to the vessel wall surface of themembrane 1015 to enhance healing of the vessel wall 1005 from injuryafter the stent 1011 is deployed. Alternatively, the agents on thevessel wall side of the membrane 1015 also encourage proliferation ofvessel wall components, for example, intima, elastic lamina, forenhancing the healing of the weakened, damaged or diseased portion ofthe vessel wall, for example, the aneurysm neck.

The agents can be effective to reduce, minimize, or prevent, immunereactions to foreign bodies. In some embodiments, agents can beeffective to attract and capture endothelial cells, or endothelialprogenitor cells, to aid in the formation of a healthy endothelium inthe region of the aneurysm being treated. The lumen side of the membranecan be configured to generally discourage factors that are involved inthrombosis.

The capture and signal agents 1021, 1022, can include, but are notlimited to, enzyme regulators tagged with antibodies or peptides,ceramides like L-PDMP, peptides, antibodies, naturally occurringmolecules, and synthetic molecules, a nucleic acid, or even apolynucleotide, if desired. Specifically, the signal agent 1022 can bean endothelial cell specific L-PDMP or an smooth muscle cell-specificD-PDMP, that can bind specifically to target molecules on endothelialcells or progenitors. Peptide or antibodies have high binding affinityand specificity for endothelial cells and progenitors. Naturallyoccurring molecules (pure or synthesized) can mimic part of the basallamina of the endothelium, so that endothelial cells or progenitors willpreferentially bind and orient on the membrane. For example,laminin-mimetic pentapeptide immobilized on the lumen surface can beeffective as a capture agent. The choice of capture agent is notconsidered to be a limitation of the disclosure. A number of moleculesor moieties will be useful in preventing blood flow to an aneurysm,while maintaining flow to perforators, and which will promote healingand/or endothelialization, while reducing the risk of thrombosis orother injury to the vessel being treated are considered to be within thescope of the disclosure.

The signal agent 1022 can also be an anti-inflammatory agent in order toreduce recruitment and infiltration of white blood cells. Thus, throughthe choice of various signal agents it is possible to enhance attachmentof endothelial cells to the membrane, while minimizing the inflammatoryresponse. The capture agent 1021 and signal agent 1022 thus actcooperatively to increase the rate of endothelialization and decreasethe during which thrombosis and restenosis might occur after the stentis expanded.

As shown in FIGS. 27 through 29, in some embodiments the stent 202 canbe used to treat a bifurcation or trituration aneurysm 201. It should benoted that the use of the device is not limited to those embodimentsthat are illustrated. The stent 202 is implanted to be partially locatedin a main artery extending to be partially located in a subordinateartery. For example, in FIG. 27, two vertebral arteries join to thebasilar artery. The stent 202 is deployed such that it is located in thebasilar artery and in a vertebral artery (right side) where the aneurysm201 is formed. On the other vertebral artery (left side), bloodcontinues to flow to the basilar artery without any obstruction sincethe membrane 203 is permeable to blood flow. Preferably, the membrane203 covers the whole stent 202, and the permeability of the membrane 203allows blood flow through the left vertebral artery (left side).Conveniently, radio-opaque markers 204 are provided in order to permitmore accurate placement of the stent 202.

In FIG. 28, the middle cerebral artery divides into the superior trunkand the inferior trunk. The stent 202 is deployed such that it islocated in the middle cerebral artery and in the inferior trunk. Again,the struts of the stent 202 do not inhibit blood flow to the superiortrunk, and blood flows through the stent 202 to the inferior trunk.

In FIG. 29, the stent 202 is deployed in the vertebral artery. As theaneurysm 201 in this example is located in a middle portion of thevertebral artery, there is no need for the stent 202 to be located inmore than one artery. When implanted, the stent 202 diverts blood flowaway from the aneurysm 201. This leads to occlusion of the aneurysm 201and keeps the arterial branches and the perforators patent. The stent202 does not require precise positioning because it is uniformly coveredwith a porous membrane 203. Thus, most of the circumferential surface ofthe stent 202 is covered by the membrane 203, and thus the vessel wallwill be uniformly contacted by the membrane in the area of the stent.

Due to the particular porosity and dimensions of the membrane 203, bloodcirculation to the aneurysm 201 is obstructed while blood supply toperforators and microscopic branches of main brain arteries as well aslarger arteries is permitted. As described earlier, obstructing bloodsupply to the aneurysm 201 isolates the aneurysm 201 from normal bloodcirculation. The aneurysm in effect “dries out.” The stent 202 andmembrane 203 thus treats the aneurysm 201 by altering the hemodynamicsin the aneurysm sac such that intra-aneurysmal thrombosis is initiated.At the same, blood flow into the arteries (branch, main, big or small)are not significantly affected by the implantation of the stent 202 orthe membrane 203 due to the special porosity of the membrane 203.Although a bifurcation aneurysm has been described, it is envisaged thatthe stent 202 may be used to treat a trituration aneurysm, or otheraneurysms, in a similar manner.

It will be appreciated by persons skilled in the art that numerousvariations and/or modifications may be made to the specific embodimentsdisclosed herein, without departing from the scope or spirit of thedisclosure as broadly described. The present embodiments are, therefore,to be considered in all respects illustrative and not restrictive of theinvention, which is defined by the claims as presented herein.

1. An endovascular device for insertion into a body vessel to treat ananeurysmal portion of the body vessel, the endovascular devicecomprising: an expandable member, expandable from a first position to asecond position, said expandable member being expandable radiallyoutwardly to the second position such that an outer surface of saidexpandable member engages with an inner surface of the vessel so as tomaintain a fluid pathway in said vessel through a lumen in theexpandable member; a membrane covering at least a portion of an outersurface of said expandable member; a plurality of pores in a poroussection of the membrane, the porous section having a substantiallyuniform porosity over a length extending from a proximal end to a distalend of the porous section, porosity being determined by a pore spacingand a pore size; wherein the proportion of the total area of an outersurface of the porous section that consists of membrane material definesa material ratio; wherein the substantially uniform porosity is selectedsuch that, when the expandable member is positioned in the body vessel,the membrane permits a flow of blood from within the lumen of theexpandable member, through at least one of the pores, and into at leastone branch vessel that branches off of the body vessel; and wherein thesubstantially uniform porosity is further selected such that, when theexpandable member is positioned in the body vessel, the membrane reducesblood flow to the aneurysmal portion of the vessel, promoting thrombosisat or in the aneurysmal portion.
 2. The device of claim 1, wherein theporosity of the porous section is selected such that it enables enhancedendothelial cell migration and tissue in-growth for endothelializationwhile substantially preventing blood circulation to the diseased,damaged or weakened portion of the vessel wall.
 3. The device of claim1, wherein the pore size is between about 1 μm and about 150 μm.
 4. Thedevice of claim 1, wherein the pore size is between about 10 μm andabout 50 μm.
 5. The device of claim 1, wherein the pore spacing isbetween about 40 μm and about 100 μm.
 6. The device of claim 1, whereinthe pore spacing is between about 60 μm and about 75 μm.
 7. The deviceof claim 1, wherein the material ratio in an as-manufactured state isbetween about 85% and about 96%.
 8. The device of claim 1, wherein thematerial ratio in a deployed state is between about 25% and about 90%.9. The device of claim 8, wherein the material ratio in the deployedstate is between about 70% and about 80%.
 10. The device of claim 8,wherein the material ratio in the deployed state is about 75%.
 11. Thedevice of claim 1, wherein a diameter of the device in the deployedstate is between about 2 mm and about 5 mm.
 12. The device of claim 1,wherein a thickness of the membrane is between about 25 μm to about 125μm.
 13. The device of claim 12, wherein the thickness of the membrane ismeasured in an as-manufactured state.
 14. The device of claim 1, whereina thickness of the membrane is between about 5 μm to about 25 μm. 15.The device of claim 14, wherein the thickness of the membrane ismeasured in a deployed state.
 16. The device of claim 1, furthercomprising at least one surface-modifying end group that promoteshealing of the body vessel after the device is inserted into the bodyvessel.
 17. The device of claim 16, wherein the at least onesurface-modifying end group comprises at least one of a fluorocarbon andthe combination of polyethylene glycol and silicon.
 18. The device ofclaim 1, further comprising at least one agent, permanently attached themembrane, that promotes healing of the aneurysm.
 19. The device of claim18, wherein the at least one permanently attached agent comprises atleast one of a peptide, a protein, an enzyme regulator, an antibody, anaturally occurring molecule, a synthetic molecule, a nucleic acid, apolynucleotide, L-PDMP, and D-PDMP.
 20. The device according to claim 1,wherein each pore has a diameter between about 30 μm and about 40 μm,and a distance between adjacent pores is between about 60 μm and about70 μm.
 21. The device of claim 1, wherein the aneurysmal portion of thevessel is located at or near at least one of an intracranial aneurysm, asaccular aneurysm, a wide-neck aneurysm, a fusiform aneurysm, acaroticocavenous fistula, an arteriovenous malformation, a carotidartery stenosis, a saphenous vein graft, a small vessel stenosis, and arenal artery repair.
 22. The device of claim 1, wherein the poroussection can be divided into n porous regions, and wherein an outersurface area of each of the n porous regions is substantially 1/n of atotal outer surface area of the porous segment, and wherein each one ofthe n porous regions has substantially the same porosity as each of theother n-1 porous regions.
 23. The device of claim 22, wherein n=2. 24.The device of claim 22, wherein n=3.
 25. The device of claim 22, whereinn=4.
 26. The device of claim 22, wherein n=5.
 27. The device of claim22, wherein the pore size is in a range between about 1 μm and about 150μm, and pore spacing is between about 10 μm and about 50 μm.
 28. Thedevice claim 22, wherein the pore size is between about 10 μm and about50 μm, and the pore spacing is between about 60 μm and about 75 μm. 29.An endovascular device system for insertion into a body vessel to treatan aneurysmal portion of the vessel, the endovascular device comprising:an expandable member, expandable from a first position to a secondposition, said expandable member being expandable radially outwardly tothe second position such that an outer surface of said expandable memberengages with an inner surface of the vessel so as to maintain a fluidpathway in said vessel through a lumen in the expandable member; amembrane covering at least a portion of an outer surface of saidexpandable member; a plurality of pores in a porous section of themembrane, the porous section having a substantially uniform porosityover a length extending from a proximal end to a distal end of theporous section, porosity being determined by a pore spacing and a poresize; wherein the proportion of the total area of an outer surface ofthe porous section that consists of membrane material defines a materialratio; wherein the substantially uniform porosity is selected such that,when the expandable member is positioned in the body vessel, themembrane permits a flow of blood from within the lumen of the expandablemember, through at least one of the pores, and into at least one branchvessel that branches off of the body vessel; and wherein thesubstantially uniform porosity is further selected such that, when theexpandable member is positioned in the body vessel, the membrane reducesblood flow to the aneurysmal portion of the vessel, promoting thrombosisat or in the aneurysmal portion; and a delivery device, operable todeliver the expandable member to the aneurysmal portion of the vessel,onto which the expandable member is loaded prior to delivery.
 30. Thesystem of claim 29, wherein the pore size is between about 1 μm andabout 150 μm.
 31. The system of claim 29, wherein the pore size isbetween about 10 μm and about 50 μm.
 32. The system of claim 29, whereinthe pore spacing is between about 40 μm and about 100 μm.
 33. The systemof claim 29, wherein the pore spacing is between about 60 μm and about75 μm.
 34. The system of claim 29, wherein the material ratio in anas-manufactured state is between about 85% and about 96%.
 35. The systemof claim 29, wherein the material ratio in a deployed state is betweenabout 25% and about 80%.
 36. The system of claim 35 wherein the materialratio in the deployed state is between about 70% and about 80%.
 37. Thesystem of claim 35, wherein the material ratio in the deployed state isabout 75%.
 38. The system of claim 29, wherein a diameter of theexpandable member in the deployed state is between about 2 mm and about5 mm
 39. The system of claim 29, wherein a thickness of the membrane isbetween about 25 m to about 125 μm.
 40. The system of claim 39, whereinthe thickness of the membrane is measured in an as-manufactured state.41. The system of claim 29, wherein a thickness of the membrane isbetween about 5 μm to about 25 μm.
 42. The system of claim 41, whereinthe thickness of the membrane is measured in a deployed state.
 43. Thesystem of claim 29 further comprising at least one surface-modifying endgroup that promotes healing of the body vessel after the device isinserted into the body vessel.
 44. The system of claim 43, wherein theat least one surface-modifying end group is at least one of afluorocarbon and the combination of polyethylene glycol and silicon. 45.The system of claim 29, further comprising at least one permanentlyattached agent to promote healing of the aneurysmal portion.
 46. Thesystem of claim 45, wherein the at least one permanently attached agentcomprises at least one of a peptide, a protein, an enzyme regulator, anantibody, a naturally occurring molecule, a synthetic molecule, anucleic acid, a polynucleotide, L-PDMP, and D-PDMP.
 47. The systemaccording to claim 29, wherein each pore has a diameter between about 10μm and about 50 μm and the distance between adjacent pores is betweenabout 60 μm and about 75 μm.
 48. The system of claim 29, wherein theaneurysmal portion of the body vessel is located at or near at least oneof an intracranial aneurysm, a saccular aneurysm, a wide-neck aneurysm,a fusiform aneurysm, a caroticocavenous fistula, an arteriovenousmalformation, a carotid artery stenosis, a saphenous vein graft, a smallvessel stenosis, and a renal artery repair.
 49. An endovascular devicefor insertion into a body vessel to treat an aneurysmal portion of abody vessel, the endovascular device comprising: means for maintaining afluid pathway in the body vessel; means for covering at least part ofthe means for maintaining, the means for covering having a substantiallyuniform porosity in a porous segment of the means for covering; andwherein, when the means for maintaining is positioned in a body vessel,the means for covering permits blood flow from the fluid pathway to atleast one branch vessel branching off the body vessel, while reducingblood flow to the aneurysmal portion, and the means for maintainingsupports the body vessel in the region of the aneurysmal portion andprovides a fluid pathway in the body vessel.
 50. A method of treating abody vessel having an aneurysmal portion, the method comprising thesteps of: providing an endovascular device, comprising: an expandablemember, expandable from a first position to a second position, saidexpandable member being expandable radially outwardly to the secondposition such that an outer surface of said expandable member engageswith an inner surface of the body vessel so as to maintain a fluidpathway in said body vessel through a lumen in the expandable member; amembrane covering at least a portion of an outer surface of saidexpandable member; a plurality of pores in a porous section of themembrane, the porous section having a substantially uniform porosityover a length extending from a proximal end to a distal end of theporous section, porosity being determined by a pore spacing and a poresize; wherein the proportion of the total area of an outer surface ofthe porous section that consists of membrane material defines a materialratio; wherein the substantially uniform porosity is selected such that,when the expandable member is positioned in the body vessel, themembrane permits a flow of blood from within the lumen of the expandablemember, through at least one of the pores, and into at least one branchvessel that branches off of the body vessel; and wherein thesubstantially uniform porosity is further selected such that, when theexpandable member is positioned in the body vessel, the membrane reducesblood flow to the aneurysmal portion of the body vessel, promotingthrombosis at or in the aneurysmal portion; and positioning theexpandable member in the body vessel.
 51. The method of claim 50,wherein the porosity of the membrane is selected such that it enhancesendothelial cell migration and tissue in-growth.
 52. The method of claim50, wherein the pore size is between about 1 μm and about 150 μm. 53.The method of claim 50, wherein the pore size is between about 10 μm andabout 50 μm.
 54. The method of claim 50, wherein the pore spacing isbetween about 40 μm and about 100 μm.
 55. The method of claim 50,wherein the pore spacing is between about 60 μm and about 75 μm.
 56. Themethod of claim 50, wherein the material ratio in an as manufacturedstate is between about 85% and about 96%.
 57. The method of claim 50,wherein the material ratio in a deployed state is between about 25% andabout 80%.
 58. The method of claim 57 wherein the material ratio in thedeployed state is between about 70% and about 80%.
 59. The method ofclaim 57, wherein the material ratio in a deployed state is about 75%.60. The method of claim 50, wherein a diameter of the expandable memberin the deployed state is between about 2 mm and about 5 mm.
 61. Themethod of claim 50, wherein a thickness of the membrane is between about5 μm to about 125 μm in the as-manufactured state.
 62. The method ofclaim 50, wherein a thickness of the membrane is between about 5 μm toabout 25 μm in the deployed state.
 63. The method of claim 50, furthercomprising providing a membrane having at least one surface-modifyingend group that encourages healing of the body vessel after the device isinserted.
 64. The method of claim 63, wherein the at least onesurface-modifying end group is at least one of a fluorocarbon and thecombination of polyethylene glycol and silicon.
 65. The method of claim50, wherein the membrane further comprises at least one permanentlyattached agent to promote healing of the aneurysm.
 66. The method ofclaim 65, wherein the at least one permanently attached agent comprisesat least one of a peptide, a protein, an enzyme regulator, an antibody,a naturally occurring molecule, a synthetic molecule, a nucleic acid, apolynucleotide, L-PDMP, and D-PDMP.